The long-term objective of our research is to determine the cellular and molecular mechanisms by which steroid hormones regulate neuronal function, including behavior. Using rats as our model system, many of our studies focus on actions of the ovarian steroids, estradiol and progesterone, in brain regions (e.g., hypothalamus, preoptic area) that regulate female reproductive physiology. A combination of in vitro and in vivo approaches are employed to examine hormonal modulation of norepinephrine, GABA and glutamate release in the hypothalamus and preoptic area as well as the mechanisms by which these neurotransmitters act in the hypothalamus to regulate female reproductive behavior. Additional studies utilizing biochemical and molecular biological techniques are investigating the hypothesis that estradiol and progesterone extensively modify noradrenergic receptor-mediated signal transduction by at least two distinct mechanisms: (1) regulation of gene transcription, most notably of the a1B -adrenoceptor, and (2) regulation of b-,a1 - and a2 -adrenoceptor coupling to G proteins that regulate effector enzymes including adenylyl cyclase and phospholipase C. To this end some of our areas of study include:

The use of molecular probes and immunoblotting to assess the effects of estradiol on cellular components that modulate receptor-G protein coupling

The examination of the influence of ovarian steroids on signaling through the nitric oxide-guanylyl cyclase pathways in the hypothalamus

Influences of ovarian hormones in brain regions not generally associated with reproductive function.

Investigation of the influence of ovarian steroids on seizure susceptibility in female rats.

Karkanias GB. Etgen AM. Estradiol reduction of the agonist high affinity form of the alpha 2-adrenoceptor in the hypothalamus of female rats: identification as the alpha 2D subtype. Molecular Pharmacology. 45(3): 509-516, 1994 Mar.